This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall goal of this project has been to identify strategies by which the immunogenicity of AIDS vaccines that are derived from Modified Vaccinia Ankara (MVA)-based viral vectors can be significantly augmented. In this reporting period, we determined that combinatorial deletion of several endogenous poxvirus immune-evasion genes from the backbone of MVA-based AIDS vaccine vectors confers an enhanced ability upon such vectors to elicit HIV-specific CD8 and CD4 T cell and antibody responses in MHC-disparate populations of rhesus macaques. The capacity of engineered MVA vectors that express SIV angtigens to elicit systemic and mucosal cellular immunity and to protect against pathogenic SIV challenge has also been investigated in Mamu-A*01-positive rhesus macaques. The development of highly immunogenic AIDS vaccine vectors from platforms other than adenovirus serotype-5 remains a high priority for the field and for future clinical assessments of the T cell hypothesis of AIDS vaccines.